title: Immunocytochemical characterization of Alzheimer disease hallmarks in APP/PS1 transgenic mice treated with a new anti-amyloid-β vaccine.
abstract: APP/PS1 double-transgenic mouse models of Alzheimer's disease (AD), which overexpress mutated forms of the gene for human amyloid precursor protein (APP) and presenilin 1 (PS1), have provided robust neuropathological hallmarks of AD-like pattern at early ages. This study characterizes immunocytochemical patterns of AD mouse brain as a model for human AD treated with the EB101 vaccine. In this novel vaccine, a new approach has been taken to circumvent past failures by judiciously selecting an adjuvant consisting of a physiological matrix embedded in liposomes, composed of naturally occurring phospholipids (phosphatidylcholine, phosphatidylglycerol, and cholesterol). Our findings showed that administration of amyloid-β₁₋₄₂ (Aβ) and sphingosine-1-phosphate emulsified in liposome complex (EB101) to APP/PS1 mice before onset of Aβ deposition (7 weeks of age) and/or at an older age (35 weeks of age) is effective in halting the progression and clearing the AD-like neuropathological hallmarks. Passive immunization with EB101 did not activate inflammatory responses from the immune system and astrocytes. Consistent with a decreased inflammatory background, the basal immunological interaction between the T cells and the affected areas (hippocampus) in the brain of treated mice was notably reduced. These results demonstrate that immunization with EB101 vaccine prevents and attenuates AD neuropathology in this type of double-transgenic mice.
authors.affiliation: Department of Neurosciences, EuroEspes Biotechnology, 15165 La Coruna, Spain.
authors.forename: Iván
authors.initials: I
authors.lastname: Carrera
authors.forename: Ignacio
authors.initials: I
authors.lastname: Etcheverría
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Lucía
authors.initials: L
authors.lastname: Fernández-Novoa
authors.forename: Valter
authors.initials: V
authors.lastname: Lombardi
authors.forename: Carmen
authors.initials: C
authors.lastname: Vigo
authors.forename: Hector H
authors.initials: HH
authors.lastname: Palacios
authors.forename: Valery V
authors.initials: VV
authors.lastname: Benberin
authors.forename: Ramón
authors.initials: R
authors.lastname: Cacabelos
authors.forename: Gjumrakch
authors.initials: G
authors.lastname: Aliev
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000235:genetics*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000276:immunology; D004195:Disease Models, Animal; D006801:Humans; D016233:Immunotherapy, Active; D051379:Mice; D008822:Mice, Transgenic; D053764:Presenilin-1 / Q000235:genetics* / Q000276:immunology
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D053764:Presenilin-1